Thesis (M.S.)--Oregon State University, 1968. / Typescript (photocopy). Includes bibliographical references (p. 57-59). Also available online.

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Physicians and scientists have suspected that the testes secrete a substance into the body that causes male secondary sexual characteristics for hundreds of years. However, testosterone was not synthesized until 1935 and it was not until the 1940's when scientists could accurately measure the amount of this hormone in the blood. Since then, scientists have been able to make correlations between the levels of testosterone in the body and men's health Scientists have long observed higher levels of testosterone to be associated with an increase in levels of Hematocrit (Hct). As a result, Testosterone Replacement Therapy (TRT) has been used to treat anemia associated with chronic diseases. In recent years, prescription sales for testosterone have sky rocketed due to new clinical uses such as androgen deficiency in older men. In fact, the rate of prescription for testosterone products has increased by over 170% in the previous five years. Long-term data shows that the level of testosterone in the male body begins to decrease at about the age of 30. As the life expectancy of the general population continues to increase, TRT may be a viable option for older men with low testosterone to increase the quality and duration of life. However, an increase in Hct continues to be a major side effect of TRT. New research is beginning to make clear the mechanism by which testosterone affects erythropoeisis. New research suggests TRT suppresses hepcidin and leads to an increase in the rate of iron (Fe) retention in red blood cells (RBCs). Inter-individual differences in the pharmacogenetic effects of TRT have been observed. In the future TRT could be genetically tailored based on the individuals DNA. In this case, the optimal dose of testosterone can be given to maximize benefits and reduce side effects. Here, the risks and benefits associated with TRT and a review of the updated Clinical Guidelines for its use will be presented. The effects of TRT on erythropoeisis will be investigated via a review of the literature. The main objective of this review is to provide a general understanding of TRT and a major side effect of its use, excessive erythropoeisis.

This thesis investigates the age - related decline in the various available measures and estimates of serum testosterone levels in men. Testosterone circulates predominantly bound with high affinity to sex - hormone binging globulin ( SHBG ) in plasma ( ~ 60 % ) and with lower affinity to albumin ( < 40 % ) ; approximately 1 - 2 % circulates unbound in plasma. It is the albumin - bound and free fractions ( termed " bioavailable testosterone " ) that are most likely to have biological effects on target tissues. This thesis reports the establishment, validation and derivation of normal ranges for an ammonium sulphate precipitation method for the measurement of bioavailable testosterone in serum. This method is in use by a number of laboratories at present including the laboratory of Professor John Morley at St Louis University with whom we collaborated. Testosterone has been shown, both cross - sectionally and longitudinally, to decline progressively beginning around the age of thirty. Total testosterone declines at approximately 0.4 % per year while bioavailable and free testosterone decline at approximately 1.2 % per year. The mechanisms that may be responsible for this include age - related changes to the hypothalamic - pituitary - testicular axis, increased SHBG levels, environmental factors, medication and chronic illness. This decline may contribute to a multitude of physiological, psychosexual and cognitive changes associated with ageing in men. This thesis crosssectionally examines the possible determinants of the various fractions of serum testosterone and the associations with various physical, psychosexual and lifestyle variables and with chronic disease and medication use. These cross - sectional data were generated from the Florey Adelaide Male Ageing study, which randomly recruited 568 men from the north and west suburbs of Adelaide, between August 2001 and August 2002. Moreover, this thesis includes a randomised controlled trial of testosterone replacement therapy in men aged 60 years and over with low - normal testosterone levels at baseline, recruited by newspaper advertisement. The goals of testosterone replacement therapy might be to prevent osteoporosis, age related frailty and falls, and to maintain optimal physical, sexual, emotional and cognitive health during the ageing process. This intervention study focused on the effect of treatment on body composition and muscle strength, symptoms of testosterone deficiency, visuospatial cognition, mood, wellbeing and quality of life. Finally, preliminary work was initiated to develop an in vitro bioassay for the measurement of serum testosterone bio - action. This was done using a transient transfection protocol in cultured cells, where androgen receptor and androgen response elements were introduced into the cells, subsequently treated with testosterone containing media and the amplitude of response quantified using a dual - luciferasereporter assay. In summary, this thesis discusses the issues with the measurement of testosterone in plasma and the factors that determine the concentration of the various fractions of testosterone in plasma. A cross - sectional study, using random recruitment procedures was used to investigate associations between testosterone levels and health - related - factors and finally a randomised - controlled - trial of testosterone replacement in ageing men with low - normal testosterone levels is reported. Throughout the thesis, the following themes are common ; body composition, physical function and strength, sexual function, lower urinary tract symptoms and the prostate, visuospatial cognition, mood, quality - of - life and wellbeing. / Thesis (Ph.D.)--Medical School, 2005.

This thesis investigates the age - related decline in the various available measures and estimates of serum testosterone levels in men. Testosterone circulates predominantly bound with high affinity to sex - hormone binging globulin ( SHBG ) in plasma ( ~ 60 % ) and with lower affinity to albumin ( < 40 % ) ; approximately 1 - 2 % circulates unbound in plasma. It is the albumin - bound and free fractions ( termed " bioavailable testosterone " ) that are most likely to have biological effects on target tissues. This thesis reports the establishment, validation and derivation of normal ranges for an ammonium sulphate precipitation method for the measurement of bioavailable testosterone in serum. This method is in use by a number of laboratories at present including the laboratory of Professor John Morley at St Louis University with whom we collaborated. Testosterone has been shown, both cross - sectionally and longitudinally, to decline progressively beginning around the age of thirty. Total testosterone declines at approximately 0.4 % per year while bioavailable and free testosterone decline at approximately 1.2 % per year. The mechanisms that may be responsible for this include age - related changes to the hypothalamic - pituitary - testicular axis, increased SHBG levels, environmental factors, medication and chronic illness. This decline may contribute to a multitude of physiological, psychosexual and cognitive changes associated with ageing in men. This thesis crosssectionally examines the possible determinants of the various fractions of serum testosterone and the associations with various physical, psychosexual and lifestyle variables and with chronic disease and medication use. These cross - sectional data were generated from the Florey Adelaide Male Ageing study, which randomly recruited 568 men from the north and west suburbs of Adelaide, between August 2001 and August 2002. Moreover, this thesis includes a randomised controlled trial of testosterone replacement therapy in men aged 60 years and over with low - normal testosterone levels at baseline, recruited by newspaper advertisement. The goals of testosterone replacement therapy might be to prevent osteoporosis, age related frailty and falls, and to maintain optimal physical, sexual, emotional and cognitive health during the ageing process. This intervention study focused on the effect of treatment on body composition and muscle strength, symptoms of testosterone deficiency, visuospatial cognition, mood, wellbeing and quality of life. Finally, preliminary work was initiated to develop an in vitro bioassay for the measurement of serum testosterone bio - action. This was done using a transient transfection protocol in cultured cells, where androgen receptor and androgen response elements were introduced into the cells, subsequently treated with testosterone containing media and the amplitude of response quantified using a dual - luciferasereporter assay. In summary, this thesis discusses the issues with the measurement of testosterone in plasma and the factors that determine the concentration of the various fractions of testosterone in plasma. A cross - sectional study, using random recruitment procedures was used to investigate associations between testosterone levels and health - related - factors and finally a randomised - controlled - trial of testosterone replacement in ageing men with low - normal testosterone levels is reported. Throughout the thesis, the following themes are common ; body composition, physical function and strength, sexual function, lower urinary tract symptoms and the prostate, visuospatial cognition, mood, quality - of - life and wellbeing. / Thesis (Ph.D.)--Medical School, 2005.

Thesis (M.S.) -- Worcester Polytechnic Institute. / Keywords: Nutraceuticals; Prostate cancer; 5-Androstenediol. Includes bibliographical references (p.71-76).

Thesis (M. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 119-138) Also available in print.

Thesis (doctoral)--University of Helsinki, 2008. / Includes bibliographical references. Also available on the World Wide Web.

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